Infectious disease is a major causal factor in the demography of human, plant and animal populations. There have been increasing calls for integrating ecological and evolutionary processes into disease management. This proposal is novel in that it combines molecular work characterizing interactions between host resistance [R] and pathogen avirulence [Avr] genes in the cultivated flax/flax rust system with extensive knowledge of a closely related wild host-pathogen system to specifically investigate the coevolution of pathogen virulence and host resistance. Population studies will focus on factors that influence among-population variation in pathogen virulence (e.g. potential for sexual recombination, short-term selection in response to population variation in host resistance). This will be combined with work examining population and regional variation in the genetic basis of host resistance, and it's epidemiological and evolutionary consequences with regard to maintenance of pathogen diversity. Detailed molecular studies (using well-developed techniques) will investigate how sequence divergence in Avr/R genes that leads to altered recognition properties affects phenotypic responses (host susceptibility vs. resistance), and how recognition is mediated. Studies at the molecular and population levels will be further integrated through work specifically aimed at characterizing phenotypic and sequence variation in one family of Avr/R genes in wild flax populations and exploring its coevolutionary implications. Together with complementary modeling work, (using extensions of previously developed spatially explicit simulations), these studies will characterize the evolutionary balance between host resistance and pathogen virulence in a natural system, and how this in turn determines patterns of disease incidence and prevalence. Relevance: There are clear epidemiological and structural similarities between plant resistance and animal innate immune systems, and similar patterns of gene diversification and selection are observed in animal MHC and plant resistance genes. Previous studies have also shown that the virulence mechanisms of pathogenic bacteria are functionally similar between plant and animal hosts, making it possible to utilize plant hosts as models for identifying virulence factors relevant to disease pathogenesis in animals and humans (Rahme et al. 2000). The experimental tractability of the Linum-Melampsora system, and the detailed molecular knowledge available, means that this project has the potential to provide major advances in our understanding of the role of genetic variation in disease, especially with respect to: (i) pathogen and host adaptation and coevolution at local and regional spatial scales;and (ii) the maintenance of genetic polymorphisms at host resistance and pathogen avirulence loci. These questions have broad relevance for understanding patterns of variation in host genes involved in pathogen recognition, as well as in the pathogen genes that are their targets.